The nature of the energy-transducing mechanism serving in support of Na ion-dependent non-electrolyte transport systems has been an area of continuing controversey. A popular concept envisions an indirect mode of energy input mediated via transmembrane monovalent ion gradients. Expenditure of metabolic energy for maintaining solute transport is considered important only for the establishment of ion gradients which subsequently determine the capability for non-electrolyte entry. Recent data from our own and several other laboratories indicates, however, that ion gradients per se may not be a sufficient criterion for establishing active solute accumulation. A form of direct expenditure of metabolic energy (ATP?) is considered necessary. This proposal represents an approach at evaluating both concepts through the use of isolated intestinal epithelial cells prepared from chick intestine. Such preparations offer significant advantages in homogeneity, opportunity for manipulating cellular ion concentrations in a defined manner, and ease of rapid sampling techniques. Experimental approaches will be followed which should provide detailed information regarding the mechanistic significance of interaction between Na ion dependent transport system for sugars and amino acids including: 1) role of Na ion gradient dissipation, 2) role of cellular ATP levels, and 3) role of steric interference between transport sites. In addition we intend to make use of ion specific ionophores for evaluating the role of specific ion gradients in maintaining transport as well as for probing the role membrane potentials might play as determinants of solute transport. Finally we consider the possibility of a physical integration between metabolic activity and plasma membrane transport systems as a fascinating but poorly evaluated concept and will endeavor to elucidate membrane functional organization of this nature.